He was a minor when his father died, but the period of his accession cannot be determined. It seems probable that it must be placed considerably before 240 BC, as Memnon tells us that he was a child at his father's death, and he had a daughter of marriageable age in 222 BC. Shortly after his accession, his kingdom was invaded by the Gauls, who were eventually repulsed.[1] After he attained manhood, he married Laodice, a sister of Seleucus II Callinicus, with whom he is said to have received the province of Phrygia as a dowry. But notwithstanding this alliance, we find Mithridates II fighting against Seleucus during a war between Seleucus and Antiochus Hierax. Eventually, Mithridates defeated Seleucus in a great battle at Ancyra in 239 BC whereby Seleucus lost twenty thousand of his troops and narrowly escaped with his own life. In 222 BC, Mithridates gave his daughter Laodice in marriage to the Seleucid king Antiochus III: another of his daughters, also named Laodice, was married about the same time to Achaeus, the cousin of Antiochus.[2]

In 220 BC, Mithridates declared war upon the wealthy and powerful city of Sinope. However, he was unable to weaken it and the city did not fall into the power of the kings of Pontus until 183 BC.[3] At an earlier period, we find Mithridates II vying with the other monarchs of Asia in sending magnificent presents to the Rhodians, after the subversion of their city by an earthquake in 227 BC.[4] The date of his death is utterly unknown. He was succeeded by Mithridates III, his son with Laodice.